Very Interesting Study showing the value of VitaminE and CoQ 10. Thanks for sending it out. Rob ----- Original Message ----- From: Kathrynne Holden, MS, RD <[log in to unmask]> To: <[log in to unmask]> Sent: Monday, May 28, 2001 4:23 PM Subject: From NPF > Dear Listfriends, > The topic of CoQ10 comes up frequently, and I thought you might be > interested in the following report, posted by Dr. Lieberman, on the NPF > list: > ============================== > > > -------------------------------------------------------------------------- ------ > > > Mitochondrial Function and Coenzyme Q10 > in Parkinson's Disease > By Cliff Shults, M.D., Professor of Neurosciences, University of > California, San Diego; Chief, Neurology Services, Veterans Affairs San > Diego, Healthcare System; and Director, National Parkinson Foundation > Center of Excellence at University of California, San Diego/Salk > Institute > > > 3-dimentional reconstruction of > a mitochondrion in a neuron in the brain > The study of mitochondrial function in Parkinson's disease (PD) was > stimulated by Dr. William Langston's discovery of a group of intravenous > drug users who had acutely developed the tremor; rigidity; and slowness > typical of Parkinson's disease after using a designer narcotic. Dr. > Langston and his colleagues determined that the chemical in the designer > narcotic responsible for the development of Parkinson's disease was > methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). To be toxic to the > dopamine-producing nerve cells in the substantia nigra (the brain cells > that are lost in PD) MPTP must first be converted in the brain to the > actual toxin, MPP+. The nerve cells in the substantia nigra are > selectively > damaged by MPP+ because the MPP+ is actively transported into those > cells. > Once inside the dopamine-producing nerve cells, the MPP+ is taken up > into > the mitochondrion, which is the part of the cells that makes energy. > MPP+ > interferes with a certain step in energy production, complex I. Through > interference with energy production and a resultant increase in the > production of oxygen free radicals, chemicals which are toxic to cells, > the > MPP+ causes damage and death of the dopamine-producing nerve cells. > > The observation that MPTP is toxic to nerve cells through interference > with > mitochondrial function led to studies of mitochondrial function in the > brains from patients with PD. Dr. Tony Schapira, working with Drs. Peter > Jenner and David Marsden in London, found that complex I activity was > selectively reduced in the substantia nigra of patients with PD. At > about > the same time, Dr. Davis Parker, who is now at the University of > Virginia, > reported a significant reduction in complex I activity in platelets from > patients with PD. Platelets are the cells in blood that cause it to > clot. > Platelets may seem an unusual tissue in which to study brain function, > but > many of the biochemical processes that occur in the brain also occur in > platelets. For example, platelets have been shown to take up dopamine, > and > they contain monoamine oxidase B (the enzyme inhibited by selegiline) > and > synuclein (the molecule involved in certain cases of familial PD). The > reports of Schapira and Parker have been subsequently confirmed by other > investigators. > > Although the studies of Schapira and Parker indicated that mitochondrial > function is reduced in the brain and platelets from Parkinson's disease > patients, the possibility remained that the reduction was due to factors > other than PD. One possible confounding factor was the level of > debilitation. It was conceivable that debilitation associated with > advanced > PD might result in reduction in platelet mitochondrial activity in a > fashion akin to the anemia caused by chronic disease. A second possible > confounding factor was drug therapy. In the studies of mitochondrial > function described above, most patients studied were receiving treatment > with levodopa. This may be of significance because Dr. Serge Przedborski > and his colleagues at Columbia University have reported that chronic > treatment of rats with levodopa caused a reversible reduction of complex > I > activity in the substantia nigra. > > Dr. Richard Haas and I at the University of California, San Diego, > reasoned > that if the reduction in complex I activity found in PD is part of the > process that results in death of dopamine-producing nerve cells in the > substantia nigra, then it should be found early in the course of the > illness. On the other hand, if the impairment in complex I activity is > due > to debilitation or medication for PD, then the activity should not be > reduced in patients with early, untreated disease. To address this > question, our group carried out two studies. First, we evaluated > mitochondrial function in platelets from a group of patients with > Parkinson's disease who had early disease and were not on medication for > PD, and from two control groups, age/sex-matched controls and spouses. > The > spouses acted as controls for the home environment. We studied > mitochondrial function in platelets from 18 PD subjects, 18 > age/sex-matched > controls and 13 spouses. We found that the activity of complex I was > significantly lower in the PD patients than in either age/sex-matched > controls or spouses. > > The first part of this study clearly showed that the reduction in the > activity of complex I defect found in platelets from patients with PD is > not due to debilitation or the effect of medication for PD. Our finding > further suggests that impaired complex I function may be part of, or the > result of, the processes that cause death of the nigral neurons. > > To evaluate the possible effects of medications that are commonly used > to > treat PD on mitochondrial function, we evaluated platelet mitochondrial > function a second time in 11 patients after the patients had received > carbidopa/ levodopa (Sinemet 25/100, one tablet three times each day) > for > one month, and a third time after the patients had received > carbidopa/levodopa and selegiline (Eldepryl, 5 mg twice each day) for an > additional month. We found that treatment with carbidopa/levodopa and > selegiline did not affect mitochondrial function in platelets. > > A goal of our research is to develop better treatments for PD > Mitochondria > produce energy in useful forms for the cells by transferring electrons > between molecules. The electron acceptor for complex I in the > mitochondria > in humans is a molecule named coenzyme Q10. Coenzyme Q10, also known as > ubiquinone, also appears to play an important role as an anitoxidant. > Antioxidants are molecules that are able to eliminate free radicals, the > molecules mentioned above that can damage cells. Coenzyme Q10's dual > functions as an integral member of the mitochondrial electron transport > chain and as an anitioxidant make it potentially important in the > treatment > of PD because evidence has accumulated that both mitochondrial > dysfunction > and damage to nerve cells in the substantia nigra due to oxidative free > radicals occur in PD. > > To further explore the possible causes of the reduction in mitochondrial > function in the Parkinson's patients, Dr. Haas, Dr. Flint Beal (formerly > of > Massachusetts General Hospital, now the Chair of the Neurology > Department > at Cornell/New York Hospital), and I measured the levels of coenzyme Q10 > in > the platelet mitochondria that have been isolated in our original study. > We > found that the level of coenzyme Q10 was significantly lower in the PD > subjects than in the control subjects, who had been matched for age and > sex. > > Dr. Beal and I next investigated whether oral administration of coenzyme > Q10 could reduce the damage caused by MPTP in one-year-old mice. As > mentioned above, MPTP is the compound discovered by Dr. Langston that > selectively injures the dopamine-producing nerve cells in the substantia > nigra. Four groups of one-year-old mice received either a standard diet > or > a diet supplemented with coenzyme Q10 for five weeks. After four weeks, > one > group that had received the standard diet and one group that had the > coenzyme Q10 supplemented diet were treated with MPTP. The four groups > continued on their assigned diets for an additional week. We found that > treatment with coenzyme Q10 did not significantly affect the levels of > dopamine in the striatum in animals that did not receive MPTP. The > striatum > is the area of the brain that the dopamine-producing nerve cells in the > substantia nigra send fibers to. In animals that received MPTP, animals > fed > coenzyme Q10 had significantly greater preservation of dopamine in the > striatum when compared to animals that received a standard diet without > coenzyme Q10. We also found that the dopaminergic nerve fibers were > significantly preserved in animals that received coenzyme Q10. Because > coenzyme Q10 had not been systematically studied in PD patients, we next > undertook a pilot study in 15 Parkinson's patients of the effects of one > month of oral coenzyme Q10 (200 mg + vitamin E 400 I two, three, or four > times/day; five subjects at each dose). We evaluated adverse events, > plasma > levels of coenzyme Q10, signs of PD, and complex I activity in platelet > mitochondria. Oral coenzyme Q10 caused a significant increase in the > plasma > level at each dose studied. Coenzyme Q10 was well tolerated, but two > subjects at the highest dose had mild changes in the urine at the end of > the study. These changes did not persist and were of uncertain clinical > significance. In 12 subjects (four subjects at each dose), the activity > of > complex I was determined at both the baseline and final visits. When the > data from all 12 subjects were analyzed together, there was a trend > toward > an increase in the activity of complex I. > > The above work stimulated development of a study to evaluate the effects > of > coenzyme Q10 in patients with early, untreated PD. Development of the > study > was a collaborative effort of Dr. Karl Kieburtz, Dr. David Oakes, Dr. > Ira > Shoulson and Sandra Plumb of the University of Rochester, Dr. Jay Nutt > of > Oregon Health Sciences University, Dr. Jorge Juncos of Emory University, > Dr. Beal, Dr. Haas, and myself. The study is supported by the National > Institute of Neurological Disorders and Stroke (NINDS), which is part of > the National Institutes of Health (NIH), under a new program to carry > out > pilot clinical trials of novel therapies for PD and other neurological > diseases. Drs. Mike Walker and Gene Oliver of NINDS have played > instrumental roles in the development of this new program, which > promises > to be very useful in bringing promising new treatments for PD into > clinical > trials. > > The study will be carried out by investigators at 12 medical centers, > all > of whom are members of the Parkinson Study Group. The Parkinson Study > Group > is a consortium of over 50 of the leading clinical centers in PD in > North > America. Persons with early PD, who do not require treatment of their PD > with levodopa or other medication, will be eligible to participate in > the > study. Patients will receive one of three doses of coenzyme Q10 (300, > 600 > or 1200 mg per day) or placebo, so each subject will have a three in > four > chance of receiving coenzyme Q10. Each patient will be followed for up > to > 17 months. Our study should indicate whether there is evidence that > coenzyme Q10 can slow the worsening that PD patients typically > experience. > > This line of research began with the clinical observation that a then > unidentified chemical (MPTP) could cause a parkinsonian syndrome, then > progressed through the research efforts of many laboratories, and has > emerged into a clinical trial of a potentially protective treatment for > PD. > The support of the National Parkinson Foundation has been very valuable > to > our group and many other groups working in this area. > > For further details regarding the study, please contact: > > Sandy Plumb > Clincal Trials Coordination Center > 1351 Hope Avenue, Suite 220, Rochester, NY 14620 > Phone: 716-275-7311 > > > > -- > Kathrynne Holden, MS, RD > Author: "Eat well, stay well with Parkinson's disease" > "Constipation and Parkinson's" -- audiocassette & guidebook > "Guidelines for Medical Nutrition Therapy for Parkinson's > disease" & Risk Assessment Tools > "Risk for malnutrition and bone fracture in Parkinson's > disease," J Nutr Elderly. V18:3;1999. > http://www.nutritionucanlivewith.com/ > > ---------------------------------------------------------------------- > To sign-off Parkinsn send a message to: mailto:[log in to unmask] > In the body of the message put: signoff parkinsn ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn